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GenSight's Optogenetic Therapy Advancing Toward Human Study

December 05, 2013

GenSight Biologics, a newly formed
gene therapy development company in France, is making significant progress in
the advancement of an optogenetic
treatment for restoring vision in people who have lost all of their
photoreceptors to retinal diseases such as retinitis
pigmentosa (RP). The company’s goal is to launch a clinical trial in
2015.

“When we formed the company, we thought about the
best approaches for reversing blindness, especially orphan conditions,” says
Bernard Gilly, Ph.D., co-founder and executive chairman at GenSight. “And
it was important for us to help patients who could suffer from blindness for 20
years or longer.”

The project is building on the advancement of a
similar therapy being developed by José-Alain Sahel,
M.D., of the Institut de la Vision, and Botond Roska, M.D., Ph.D., of the
Friedrich Miescher Institute — an effort funded through the Foundation’s
Translational Research Acceleration Program (TRAP). Established in 2008,
the goal of TRAP is to expedite the advancement of promising retinal-disease
treatments into human studies. Twenty million dollars is targeted annually for
TRAP-funded projects.

Optogenetics is an emerging therapeutic approach
that involves the delivery of genes to cells of the retina, brain or other
neural tissue to make them light-sensitive. In addition to being developed for
retinal diseases, optogenetics shows potential for treating Parkinson’s
disease, sleep disorders, depression and other neurological conditions. By
making neural cells light-sensitive, they can be controlled to minimize or
reverse symptoms.

The GenSight optogenetic treatment uses an
adeno-associated virus (AAV) for delivery of a gene expressing halorhodopsin, a
light-sensitive protein similar to rhodopsin, which is naturally
produced in photoreceptors to make vision possible. The treatment is
administered to either non-functional photoreceptors or, in cases where
photoreceptors have been completely lost, to inner retinal cells, such as
bipolar cells,
which often survive in advanced diseases.

Dr. Gilly says that a visual interface — a pair
of high-tech glasses with a camera — is also being developed by GenSight to
enhance the visual experiences of patients receiving the optogenetic gene
therapy. In simple terms, the interface provides some of the visual processing
functions that photoreceptors would normally provide, and it also delivers
light to bipolar cells in a wavelength that activates halorhodopsin.

Researchers have thus far demonstrated that the
treatment elicits visual behavior in a mouse model of advanced retinal
degeneration as well as light sensitivity in a culture of human retinal cells.
“We believe this is a very strong proof of concept,” says Dr. Gilly.

In preparation for a clinical trial, toxicology
studies will be performed. GenSight will also produce the treatment using good
manufacturing practices to ensure that it meets quality and safety standards
for use in humans.

While the therapy will initially be studied in
humans with rare, inherited retinal diseases, Dr. Gilly says the company would
also like to eventually make it available to people with age-related macular
degeneration.